It is proposed to investigate the details and significance of a newly detected conformational signal from hemoglobin. The signal is the emission of the tryptophyl residues, quenched by energy transfer to the heme. It is detectible by measuring the lifetimes of the emission of the tryptophans on the picosecond time-scale. The signal is ligand sensitive, however this cannot be explained by modifications of the electronic spectra of the hemes upon ligand binding. Therefore, it appears to reflect only the quenching produced by the relative positions of the tryptophyl residues and the heme in the molecule, and it offers a means for following modifications of the relative positions of heme and tryptophans (here defined as heme "conformation") in the molecule. The signal may reflect only local conformational dynamics of the tryptophans and of the heme, or it may be a conformational marker for the T and R states of hemoglobin. The local effects will be explored by observing: 1) The influence on this signal of the Beta37 tryptophan (at the alphal Beta2 interface) will be investigated in hemoglobin Rotschild (Beta37 Trp- greater than arg) and Hirose (Beta37 Trp- greater than Ser). 2) The influence of the chemical structure of the heme will be approached utilizing hemoglobins where the natural heme has been substituted with deutero-, meso- and spyrographis- heme. The influence of the metal atom will be investigated using mangano-, zinc-, and cobalt- hemoglobins. The possibility that it is a marker for the R and T states will be investigated by: 3) Protein dynamics simulations, which will explore the details of the energy transfer between heme and tryptophans as due to the relative positions and motions of the residues, in the presence and absence of ligands. 4) Measuring the signal in "frozen" hemoglobin systems, where the allosteric properties have been eliminated, as, for example, in CPA digested hemoglobins. 5) Testing the influence of the alpha-beta interaction in the isolated subunits of normal hemoglobin, of the mutant hemoglobin Rotschild and Hirose, and of heme substituted hemoglobins. 6) Titrating the signal in solutions of hemoglobin progressively saturated with ligands and in hybrid molecules (e.g. iron-cobalt hemoglobin hybrids) where only one kind of subunit can combine with ligands.